Solvent addition and removal in the hydrogenation of catmint oil

ABSTRACT

Disclosed are methods for treating catmint oil. The treated catmint oil can be used for the production of hydrogenated catmint oil, which is enriched in the insect repellent, dihydronepetalactone, and from which formulated products may be prepared.

This application is a continuation of, and claims the benefit of, U.S.application Ser. No. 12/520,173, filed 18 Jan. 2010; which is the U.S.national stage application of Intl. Application No. PCT/US07/25984,filed 20 Dec. 2007; which claimed the benefit of U.S. ProvisionalApplication No. 60/876,563, filed 21 Dec. 2006, and U.S. ProvisionalApplication No. 60/876,565, filed 21 Dec. 2006; each of which is by thisreference incorporated in its entirety as a part hereof for allpurposes.

TECHNICAL FIELD

The present invention relates to the hydrogenation of the essential oilof the catmint plant, Nepeta cateria. The hydrogenation of the essentialoil provides an enriched source of the insect repellent,dihydronepetalactone.

BACKGROUND

Dihydronepetalactone (DHN) has been shown to be an effective insectrepellent, as discussed in U.S. Ser. No. 05/112,166.Dihydronepetalactone can be produced by hydrogenating nepetalactone, acomponent of the essential oil from the catmint plant, Nepeta cataria(herein referred to as catmint oil). Catmint oil can be purified fromplants of the N. cataria by various isolation processes including steamdistillation [Regnier, F. E. et al, Phytochemistry (1967) 6:1281-1289],organic solvent extraction, microwave-assisted organic solventextraction, supercritical fluid extraction, mechanical extraction andenfleurage (initial cold extraction into fats followed by organicsolvent extraction). The catmint oil so obtained can be used in thecrude form to produce DHN, however the hydrogenation reaction can beadversely affected by undesirable components contaminating the crudecatmint oil.

Nepetalactone has been purified from catmint oil by crystallization[Regnier, F. E. et al, Phytochemistry (1967) 6:1271-1280], howevercrystallization is expensive, and on the potential scale required forcommercialization, it is uneconomical. Therefore, it would be highlydesirable to produce a catmint oil with improved properties, such thathigh yields of the insect repellent DHN may be produced.

SUMMARY

This invention relates to processes for preparing hydrogenated catmintoil, processes for preparing products that are formulated therefrom, theuse of such processes, and the products obtained and obtainable by suchprocesses.

In one embodiment of the processes hereof, there is provided a processfor preparing hydrogenated catmint oil by (a) distilling crude catmintoil to produce (i) a distillate fraction comprising volatile componentsdriven off from the beginning amount of crude catmint oil, and (ii) apot fraction; and (b) contacting the pot fraction of step (a) withhydrogen and a hydrogenation catalyst to produce hydrogenated catmintoil.

In another embodiment of the processes hereof, there is provided aprocess for preparing hydrogenated catmint oil by (a) distilling crudecatmint oil to produce (i) a distillate fraction comprising volatilecomponents driven off from the beginning amount of crude catmint oil,and (ii) a pot fraction; and (b) contacting the pot fraction of step (a)with hydrogen and a hydrogenation catalyst to produce hydrogenatedcatmint oil; wherein one or both of steps (a) and (b) are conducted inthe presence of a solvent.

In a further embodiment of the processes hereof, there is provided aprocess for preparing a product formulated from a hydrogenated catmintoil by (a) distilling a beginning amount of crude catmint oil to produce(i) a distillate fraction comprising volatile components driven off fromthe beginning amount of crude catmint oil, and (ii) a pot fraction; (b)contacting the pot fraction of step (a) with hydrogen and ahydrogenation catalyst to produce hydrogenated catmint oil; and (c)incorporating the hydrogenated catmint oil produced in step (b) into aformulated product for application to the skin, hide, hair, fur orfeathers of a human or a domesticated animal; wherein the distillationof step (a) and/or the hydrogenation of step (b) is conducted in thepresence of a solvent.

In yet another embodiment of the processes hereof, there is provided ahydrogenated catmint oil that comprises a 9S dihydronepetalactone.

In yet another embodiment of the processes hereof, a hydrogenatedcatmint oil may be prepared by (a) distilling a beginning amount ofcrude catmint oil to produce (i) a distillate fraction comprisingvolatile components driven off from the crude catmint oil, wherein theweight of the distillate fraction comprises about 2% to about 20% of theweight of the beginning amount of crude catmint oil, and (ii) a potfraction; (b) contacting the pot fraction produced in step (a) withhydrogen and a hydrogenation catalyst to produce hydrogenated catmintoil; and (c) optionally, recovering the hydrogenated catmint oil of step(b).

In yet another embodiment of the processes hereof, a hydrogenatedcatmint oil may be prepared by (a) distilling a beginning amount ofcrude catmint oil that has at least about 150 ppm of sulfur-containingcompounds to produce (i) a distillate fraction that comprises at leastabout 8 wt % of the amount of sulfur-containing compounds in thebeginning amount of crude catmint oil, and (ii) a pot fraction; (b)contacting the pot fraction produced in step (a) with hydrogen and ahydrogenation catalyst to produce hydrogenated catmint oil; and (c)optionally, recovering the hydrogenated catmint oil of step (b).

DETAILED DESCRIPTION

This invention relates to processes for preparing hydrogenated catmintoil, processes for preparing products that are formulated therefrom, andthe formulated products obtained thereby. Important aspects of thisinvention therefore relate to methods for treating the essential oil ofthe catmint plant, Nepeta cataria, herein referred to as catmint oil.Methods for treating catmint oil include distillation and/or treatmentwith an oxidizing agent. The treated catmint oil so produced can be usedin a hydrogenation reaction to produce hydrogenated catmint oil, whichis enriched in the insect repellent, dihydronepetalactone. DHN in turnmay be used for the purpose of preparing a formulated product forapplication to the skin, hide, hair, fur or feathers of a human or adomesticated animal.

DEFINITIONS

In the description of the processes hereof, the following definitionalstructure is provided for certain terminology as employed in variouslocations in the specification:

The structures of 9S dihydronepetalactone stereoisomers are shown below.

The term “nepetalactone” as used herein refers to the compound havingthe general structure of Formula I:

The term “dihydronepetalactone” (“DHN”) as used herein refers to thecompound having the general structure of Formula II:

The term “puleganic acid” as used herein refers to the compound havingthe general structure of Formula III:

The term “nepetalic acid” as used herein refers to the compound havingthe general structure of Formula IV:

The term “crude catmint oil” as used herein refers to catmint oil thathas been obtained from the catmint plant, N. cataria, and containspredominantly the trans-cis and/or cis-trans isomers of nepetalactone asshown in Formulae V and VI, respectively.

Crude catmint oil may also contain extraneous components such ascaryophyllenes, carvones, limonenes and other sesquiterpenes, and otherunidentified impurities. One or more of these extraneous components candecrease the effectiveness of the hydrogenation of catmint oil, asmeasured for example by the rate of conversion of the nepetalactonetherein to dihydronepetalactone. The distillation steps of the processeshereof can assist with the removal of one or more of the extraneouscomponents, thereby improving the hydrogenation of catmint oil.

In one embodiment of the processes hereof, there is provided a processfor preparing hydrogenated catmint oil by (a) distilling crude catmintoil to produce (i) a distillate fraction comprising volatile componentsdriven off from the beginning amount of crude catmint oil, and (ii) apot fraction; and (b) contacting the pot fraction of step (a) withhydrogen and a hydrogenation catalyst to produce hydrogenated catmintoil.

In one particular embodiment hereof, a hydrogenated catmint oil may beprepared by (a) distilling a beginning amount of crude catmint oil toproduce (i) a distillate fraction comprising volatile components drivenoff from the crude catmint oil, wherein the weight of the distillatefraction comprises about 2% to about 20% of the weight of the beginningamount of crude catmint oil, and (ii) a pot fraction; (b) contacting thepot fraction produced in step (a) with hydrogen and a hydrogenationcatalyst to produce hydrogenated catmint oil; and (c) optionally,recovering the hydrogenated catmint oil of step (b).

In another embodiment the distillate fraction has about 5% to about 10%by weight of the beginning amount of crude catmint oil.

Depending on the process used to obtain catmint oil from N. cataria, theextraneous components contained in catmint oil can comprisesulfur-containing compounds, dimethyl sulfide for example, that maydecrease the rate of conversion of nepetalactone, possibly by poisoningthe hydrogenation catalyst. Sulfur-containing compounds present in thecrude catmint oil can be quantitated using X-ray fluorescencespectroscopy.

In another embodiment hereof, a hydrogenated catmint oil may be preparedby (a) distilling a beginning amount of crude catmint oil that has atleast about 150 ppm of sulfur-containing compounds to produce (i) adistillate fraction that comprises at least about 8 wt % of the amountof sulfur-containing compounds in the beginning amount of crude catmintoil, and (ii) a pot fraction; (b) contacting the pot fraction producedin step (a) with hydrogen and a hydrogenation catalyst to producehydrogenated catmint oil; and (c) optionally, recovering thehydrogenated catmint oil of step (b).

In more specific embodiments, the distillate fraction of step (a)comprises at least about 25%, at least about 50% or at least about 75%of the sulfur-containing compounds by weight relative to the beginningamount of sulfur-containing compounds in the crude catmint oil.

Distillation is a well-known process [see, for example, Seader et al,“Distillation”, in Perry's Chemical Engineers' Handbook, 7^(th) Ed.(1997) McGraw-Hill, Section 13]. Distillation methods suitable for thecurrent process include vacuum distillation, steam distillation andsolvent distillation. Both steam and solvent distillation can optionallybe performed under vacuum. Distillation of crude catmint oil can becarried out using any suitable apparatus, such as a pot or resin kettleoutfitted with a heating element, a shell and tube condenser, and a dryice finger. The temperature at which distillation and condensation occurwill depend on the process used. For example, the heating temperaturewill be lower when vacuum is applied during the distillation process.

When steam distillation is utilized, approximately 2% to about 40% water(by weight relative to the weight of the catmint oil plus the water) maybe added to the catmint oil. In a more specific embodiment,approximately 5% to about 20% water (by weight relative to the weight ofthe catmint oil plus the water) may be added to the catmint oil. In oneembodiment, the mixture of catmint oil and water can be distilled at atemperature of about 100° C., i.e. the boiling point of the water, atatmospheric pressure. In an alternative embodiment, the distillation canbe performed at an absolute pressure of less than or equal to about 68.9kPa. In yet another embodiment, the distillation can be performed at anabsolute pressure of less than or equal to about 41.4 kPa. At lowerpressures, the distillation temperature will be lower due to the lowerboiling point of water at reduced pressure.

Solvent distillation refers to a distillation process whereby a solventis added to aid in the separation of components of close-boilingmixtures. “Close-boiling” mixtures are mixtures wherein the boilingpoints of the components are similar. In this invention, the solventused is typically more volatile than the catmint oil, and when distilledoff, removes some of the volatile species present in the crude oil.Preferably the solvent is a compound that is inert to the catmint oil.Solvents suitable for this invention include C₁ to C₅ straight-chain orbranched alcohols. In one embodiment, the solvent is an alcohol selectedfrom the group consisting of methanol, ethanol, isopropanol andn-propanol.

Preferably, the initial solvent concentration is from about 5% to about60% by weight relative to the combined weight of the catmint oil plusthe solvent. In another embodiment, the initial solvent concentration isfrom about 10% to about 25% by weight relative to the combined weight ofthe catmint oil plus the solvent. Solvent distillation can be performedat atmospheric pressure. In an alternative embodiment, the distillationis performed at an absolute pressure of less than or equal to about 68.9kPa. In yet another embodiment, the distillation is performed at anabsolute pressure of less than or equal to about 41.4 kPa. Thetemperature at which solvent distillation is carried out will depend onparameters such as the solvent used, the concentration of the solvent,and the pressure at which the distillation is carried out. Typicaltemperatures range from about 50° C. to about 100° C.

In a further embodiment of this invention, solvent distillation can becombined with steam distillation. For example, one could carry out steamdistillation of crude catmint oil as described above to obtain a catmintoil from which some of the volatile components and most of the waterhave been removed. In a second distillation step, this steam distilledcatmint oil is then contacted with a solvent, and solvent distillationis performed as described above. Solvent distillation will removeadditional volatile components not removed by steam distillation. Inaddition, solvent distillation can be used to remove residual waterintroduced into the catmint oil during steam distillation.

At temperatures above about 80° C., nepetalactone isomers in wet catmintoil may hydrolyze to undesirable products, such as nepetalic acid. Therate of hydrolysis increases with temperature up to about 200° C., wherethe catmint oil thermally degrades. Therefore, it would be desirable tobe able to carry out the distillation of catmint oil at a lowertemperature to avoid the hydrolysis of nepetalactone. The temperaturecan be reduced by operating the distillation apparatus under vacuum. Theamount of vacuum applied to the system will depend on the systemcomponents, however achieving a vacuum of less than about 68.9 kPa(absolute) is preferred. In one embodiment, vacuum distillation isperformed at an absolute pressure of less than about 6.89 kPa.

In a further embodiment, a step of contacting crude catmint oil with anoxidizing agent can be performed before a step of distillation, asdescribed above, is performed.

Examples of oxidizing agents suitable for use herein to contact withcrude catmint oil include Na₂B₄O₇.10H₂O, which is available for examplein a product such as 20 Mule Team® Borax. In one embodiment, contactingcan occur by mixing the catmint oil with Na₂B₄O₇.10H₂O, followed byfiltering the mixture to separate the Na₂B₄O₇.10H₂O from the oxidizedcatmint oil. In an alternative embodiment, the Na₂B₄O₇.10H₂O can beplaced in a column, and the crude catmint oil can be drained through thecolumn. Na₂B₄O₇.10H₂O can be used at a concentration of about 1% toabout 50% by weight relative to the combined weight of the Na₂B₄O₇.10H₂Oplus the catmint oil. In more specific embodiments, Na₂B₄O₇.10H₂O can beused at concentrations of about 3% to about 50% and about 15% to about50% by weight relative to the combined weight of the Na₂B₄O₇.10H₂O plusthe catmint oil.

Other suitable oxidizing agents for use to contact with crude catmintoil include a hydrogen peroxide solution, which can be used at aconcentration of about 1% to about 15% relative to the combined weightof the hydrogen peroxide solution plus the catmint oil. A 30% hydrogenperoxide solution has been found suitable. The mixture of hydrogenperoxide and catmint oil are vigorously agitated, and the aqueoushydrogen peroxide phase is allowed to separate from the organic catmintoil phase. The catmint oil phase can be recovered from the aqueoushydrogen peroxide phase by decantation. Contacting of crude catmint oilwith Na₂B₄O₇.10H₂O or a dilute hydrogen peroxide solution can beperformed at room temperature (about 25° C.).

Ozone is yet another alternative oxidizing agent, which can be used byvigorously agitating the crude catmint oil in the presence of ozone.

Examples of the performance of the above described methods of distillingand purifying crude catmint oil are described in U.S. ProvisionalApplication No. 60/876,569, which is incorporated in its entirety as apart hereof for all purposes.

Crude catmint oil can be obtained from a supplier such as George ThackerSons (Alberta, Canada), or can be obtained from catmint plant materialby known methods, such as distillation [Regnier, F. E. et al,Phytochemistry (1967) 6:1281-1289]. One particular method for obtainingcatmint oil suitable for use herein includes the steps of (a) contactingplant material with steam whereby a volatilized heterogeneous mixturecomprising catmint oil and water is formed; (b) condensing thevolatilized heterogeneous mixture to form a heterogeneous liquidcondensed mixture comprising catmint oil and water; (c) contacting theheterogeneous liquid condensed mixture of step (b) with sufficient saltsuch that (1) the resulting mixture has a ratio[(ρ_(catmint oil)−ρ_(aqueous solution))/μ_(aqueous solution)] of lessthan or equal to about −0.05, (2) the resulting solubility of thecatmint oil in the salt solution decreases by at least about 50%, or (3)a combination of (1) plus (2), thereby causing the heterogeneous liquidcondensed mixture to separate into a catmint oil phase and an aqueoussalt solution phase; and (d) recovering the catmint oil phase of step(c). This method is more particularly described in U.S. ProvisionalApplication No. 60/876,556, which is incorporated in its entirety as apart hereof for all purposes.

Following distillation, and optional contact with an oxidizing agent,the pot fraction containing catmint oil can be used in a hydrogenationreaction to obtain hydrogenated catmint oil. The hydrogenation reactionmay be carried out in the presence of hydrogen at a temperature of about−10° C. to about 200° C. The hydrogen pressure for the reaction isgenerally from about 0.1 MPa to about 20.7 MPa. The time, temperature,hydrogen pressure and flow rate and feed may be adjusted, according toknown principles, to obtain optimal conversion of hydrogenation ofcatmint oil using a given catalyst. A suitable hydrogenation reaction isthat which is described in U.S. Pat. No. 7,067,677 (which isincorporated in its entirety as a part hereof for all purposes).Described therein is the hydrogenation of nepetalactone in the presenceof a catalytic metal that is not nickel, platinum or palladium. Theprocess can be carried out at a temperature of about 25° C. to about250° C. at a hydrogen pressure of about 0.1 MPa to about 20 MPa. Othersuitable processes for making a dihydronepetalactone include a processas described in U.S. Provisional Application No. 60/876,568, which isincorporated in its entirety as a part hereof for all purposes. Ahydrogenation reaction may be carried out in batch in a single reactor,in sequential batch in a series of reactors, in reaction zones withinone or more reactors, or in continuous mode in any of the equipmentcustomarily employed for continuous processes.

In another embodiment of this invention, the processes hereof provide ahydrogenated catmint oil that comprises a 9S dihydronepetalactone.

A particular embodiment of the processes hereof includes a process forpreparing hydrogenated catmint oil by (a) distilling crude catmint oilto produce (i) a distillate fraction comprising volatile componentsdriven off from the beginning amount of crude catmint oil, and (ii) apot fraction; (b) contacting the pot fraction of step (a) with hydrogenand a hydrogenation catalyst to produce hydrogenated catmint oil;wherein one or both of steps (a) and (b) are conducted in the presenceof a solvent. Suitable solvents for either or both such purposes includeC₁ to C₅ straight-chain or branched alcohols, such as an alcoholselected from the group consisting of methanol, ethanol, isopropanol andn-propanol.

In the above process, the distillation of step (a), or the hydrogenationof step (b), or both steps may be conducted in the presence of asolvent. Solvent may be added to the pot fraction produced by step (a)before it is hydrogenated in step (b), or solvent may be present in thehydrogenated catmint oil produced in step (b), and the process mayfurther include a step of removing solvent from the hydrogenated catmintoil produced in step (b). When solvent removal occurs, the process mayfurther include a step of recycling removed solvent to the distillationof step (a) and/or the hydrogenation of step (b).

When the hydrogenation of step (b) is conducted in the presence ofsolvent, it may be conducted in a plurality of steps, reactor zones orreactors, and solvent may be removed between one step, zone or reactorand the next succeeding step, zone or reactor. As noted above, theprocess may in such case also include a step of recycling removedsolvent to the distillation of step (a) and/or the hydrogenation of step(b).

The embodiment of the processes hereof described above may also includea step of incorporating the hydrogenated catmint oil produced in step(b) into a formulated product for application to the skin, hide, hair,fur or feathers of a human or domesticated animal.

Another alternative embodiment of the processes hereof also includes astep of incorporating hydrogenated catmint oil into a formulated productfor application to the skin, hide, hair, fur or feathers of a human ordomesticated animal; and generally involves the following steps:

-   -   (a) distilling a beginning amount of crude catmint oil to        produce (i) a distillate fraction comprising volatile components        driven off from the beginning amount of crude catmint oil,        and (ii) a pot fraction;    -   (b) contacting the pot fraction of step (a) with hydrogen and a        hydrogenation catalyst to produce hydrogenated catmint oil; and    -   (c) incorporating the hydrogenated catmint oil produced in        step (b) into a formulated product for application to the skin,        hide, hair, fur or feathers of a human or domesticated animal;    -   wherein the distillation of step (a) and/or the hydrogenation of        step (b) is conducted in the presence of a solvent.        Solvents suitable for use in this embodiment include those noted        above.

This embodiment of the processes may also include a step ofincorporating a solvent into the formulated product, which may be doneby adding solvent to the distillation that occurs during step (a),adding solvent to the hydrogenation that occurs during step (b), oradding solvent in both such steps.

In this embodiment, incorporation of solvent into the formulated productmay include any two of, or all three of, the steps of (i) adding solventto the distillation that occurs in step (a), (ii) adding solvent to thehydrogenation that occurs during step (b), and (ii) adding solvent tothe hydrogenated catmint oil that is obtained as the product of step(b). The same solvent may be used in all steps. For example, thehydrogenation of step (b) may be conducted in a plurality of steps,reactor zones or reactors, and, in such case, the incorporation ofsolvent into the formulated product comprises a step of adding solventto the hydrogenation that occurs in some but not all, or in all, of thesteps, zones or reactors.

Following the hydrogenation reaction, the hydrogenated catmint oil canbe recovered from the reaction mixture by known methods of separation,such as decantation or filtration. Dihydronepetalactone can be recoveredfrom the hydrogenated catmint oil, for example, by columnchromatography.

The processes hereof for distilling and hydrogenating catmint oilprovide Hydrogenation Reaction Products (“HRP”). As hydrogenated catmintoil in the form of an HRP may be incorporated into a formulated productfor application to the skin, hide, hair, fur or feathers of a human ordomesticated animal, this invention relates further to compositionscomprising HRP, and to the use of HRP and the compositions thereof. Thepreparations of this invention, which include the HRP compoundsdescribed above, and the compositions, formulations and other materialsthat may be prepared from such compounds according to this invention,and mixtures thereof, may all be used for a multiplicity of purposes.These purposes include, for example, use as an active ingredient in aneffective amount for the repellency of various insect or arthropodspecies, use as a fragrance compound itself or as an ingredient in aperfume composition, or use as a topical treatment for skin.

For example, the preparations hereof may be applied in a topical mannerto the skin, hide, hair, fur, feathers or other surface of a mammal,such as a human or domesticated animal, that serves as a host for aninsect or arthropod. Living, animate hosts such as these may serve asinsect-acceptable food sources for blood-feeding insects and arthropodssuch as biting flies, chiggers, fleas, mosquitoes, ticks and lice.

The preparations hereof may also be applied to or incorporated into aninanimate host for an insect or arthropod, which includes for example afood source such as growing or harvested plants or crops, or a desirablehabitat such as a building or structure, or other types of protectivearticles such as may be made from fabrics or textiles. Such inanimatehosts may include, for example, towers, silos, bins, hoppers, boxes andbags in which food products such as grain is stored, which may be anattractive habitat or food source for insects such as flour or beanbeetles or weevils. A preparation hereof may be used to repel suchinsects by applying the preparation to a container or article or to anypoint of access thereto.

The preparations hereof may also be applied to the skin and/or hair ofhumans to impart a pleasant odor or aroma as a fragrance compounditself, or as an ingredient in a perfume composition; and thepreparations hereof may also be used as a topical treatment for skin byapplication to the skin and/or hair of humans in the form of a bodywash, rinse, conditioner, toner, lotion, splash, spray or other type ofcosmetic product as applied personally by the user.

A repellent substance drives insects or arthropods away from theirpreferred hosts, whether animate or inanimate, or renders those hostsunacceptable in some manner. Most repellents are not active poisons, butrather make desirable insect/arthropod hosts, or the conditionsassociated with those hosts, unattractive or offensive. Typically, arepellent is a preparation that can be topically applied to, on or abouta host, or can be incorporated into a host, to deter insects/arthropodsfrom approaching or remaining in the nearby 3-dimensional space in whichthe host exists. In either case, the effect of the repellent is to causethe insects/arthropods to reject the host, or to cause them to be drivenout of and away from the host, which thereby minimizes the frequency of“bites” to an animate host, or minimizes the amount of damage that theinsect/arthropod causes to an inanimate host. Repellents may be in theform of gases (olfactory), liquids, or solids (gustatory).

One property that is important to overall repellent effectiveness issurface activity, as many repellents contain both polar and non-polarregions in their structure. A second property is volatility. Repellentsform an unusual class of compounds where evaporation of the activeingredient from a surface of, on or near a host makes an importantcontribution to its effectiveness, as measured by the protection of ananimate host from bites or the protection of an inanimate host fromdamage.

An aspect of the potency of a repellent substance is the extent to whichthe concentration of the substance in the air space above or around asurface where it has been applied is sufficient to repel an insect orarthropod, particularly a flying insect. A desirable level ofconcentration of the repellent is obtained in the air space primarilyfrom evaporation, but the rate of evaporation is affected by the rate ofany absorption into the surface, and penetration into and through thesurface is thus almost always an undesirable mode of loss of repellentfrom the surface. This consideration applies equally to the loss of arepellant by absorption into the skin or other surface of an animatehost as to the loss of a repellant from a surface of an inanimate hostmade from a synthetic material, where the repellant substance mayundesirably react with other chemicals present on that same surface.Loss of concentration of a repellant substance by physical action, suchas dilution or absorption, or loss of concentration by chemical action,such as a reaction, is equally undesirable in the case of repellency ofan insect/arthropod that crawls, for which concentration directly on asurface is an important factor.

In selecting a substance for use as an insect/arthropod repellentactive, the inherent volatility of the substance thus is generally animportant consideration. A variety of strategies are available, however,when needed for the purpose of attempting to increase persistence of theactive while not decreasing, and preferably increasing, volatility. Forexample, the active can be formulated with polymers and inertingredients to increase persistence on a surface to which applied orfrom which it will be exuded. The presence of inert ingredients in theformulation, however, dilutes the active in the formulation, and theloss of an active from undesirably rapid evaporation must thus bebalanced against the risk of simply applying too little active to beeffective. Alternatively, the active ingredient may be contained inmicrocapsules to control the rate of loss from a surface or an article;a precursor molecule, which slowly disintegrates on a surface or in anarticle, may be used to control the rate of release of the activeingredient; or a synergist may be used to continually stimulate theevaporation of the active from the formulated composition.

The release of an active ingredient that is intended for application tothe skin or other surface of an animate host may be accomplished, forexample, by sub-micron encapsulation, in which the active ingredient isencapsulated or enveloped in a skin-nourishing protein. The protein maybe used, for example, at about a 20 wt % concentration. An applicationof repellent contains many of these protein capsules that may besuspended in either a water-based lotion, or water for sprayapplication. After contact with skin, the protein capsules begin tobreak down, releasing the encapsulated active. The process continues aseach microscopic capsule is depleted then replaced in succession by anew capsule that contacts the surface and releases its activeingredient. The process may take up to 24 hours for one application.Because a protein adheres very effectively to skin, these formulationsare very resistant to perspiration (sweat-off) and dilution by waterfrom other sources.

One of the distinct advantages of the preparations of this invention isthat they are all characterized by a relative volatility that makes themsuitable for use to obtain a desirably high level of concentration ofactive ingredient on, above and around a surface of an animate orinanimate host, as described above. One or more of these preparationsmay be used for such purpose as an active, or an active formulation, ina composition in which the preparation is admixed with a carriersuitable for wet or dry application of the composition to a surface inthe form, for example, of a liquid, aerosol, gel, aerogel, foam orpowder (such as a sprayable powder or a dusting powder). Suitablecarriers include any one of a variety of commercially available organicand inorganic liquid, solid, or semi-solid carriers or carrierformulations usable in formulating a variety of cosmetic products. Whenformulating a composition for application to the skin or other surfaceof a human, it is important to select a dermatologically acceptablecarrier. A carrier suitable for use herein may include water, alcohol,silicone, petrolatum, lanolin; or may include an organic liquid carriersuch as a liquid aliphatic hydrocarbon (e.g. pentane, hexane, heptane,nonane, decane and their analogs) or a liquid aromatic hydrocarbon.

Examples of other useful liquid hydrocarbons include oils produced bythe distillation of coal and the distillation of various types andgrades of petrochemical stocks, including kerosene oils that areobtained by fractional distillation of petroleum. Suitable petroleumoils include those generally referred to as agricultural spray oils(e.g. the so-called light and medium spray oils, consisting of middlefractions in the distillation of petroleum and which are only slightlyvolatile). Such oils are usually highly refined and may contain onlyminute amounts of unsaturated compounds. Such oils, moreover, aregenerally paraffin oils and accordingly can be emulsified with water andan emulsifier, diluted to lower concentrations, and used as sprays. Talloils, obtained from sulfate digestion of wood pulp, like the paraffinoils, can similarly be used. Other organic liquid carriers can includeliquid terpene hydrocarbons and terpene alcohols such as alpha-pinene,dipentene, terpineol, and the like.

Other suitable carriers include silicone, petrolatum, lanolin, liquidhydrocarbons, agricultural spray oils, paraffin oil, tall oils, liquidterpene hydrocarbons and terpene alcohols, aliphatic and aromaticalcohols, esters, aldehydes, ketones, mineral oil, higher alcohols,finely divided organic and inorganic solid materials. In addition to theabove-mentioned liquid hydrocarbons, the carrier can containconventional emulsifying agents which can be used for causing the activeingredient to be dispersed in, and diluted with, water for end-useapplication. Still other liquid carriers can include organic solventssuch as aliphatic and aromatic alcohols, esters, aldehydes, and ketones.Aliphatic monohydric alcohols include methyl, ethyl, normal-propyl,isopropyl, normal-butyl, sec-butyl, and tert-butyl alcohols. Suitablealcohols include glycols (such as ethylene and propylene glycol) andpinacols. Suitable polyhydroxy alcohols include glycerol, arabitol,erythritol, sorbitol, and the like. Finally, suitable cyclic alcoholsinclude cyclopentyl and cyclohexyl alcohols.

Conventional aromatic and aliphatic esters, aldehydes and ketones can beused as carriers, and occasionally are used in combination with theabove-mentioned alcohols. Still other liquid carriers include relativelyhigh-boiling petroleum products such as mineral oil and higher alcohols(such as cetyl alcohol). Additionally, conventional or so-called“stabilizers” (e.g. tert-butyl sulfinyl dimethyl dithiocarbonate) can beused in conjunction with, or as a component of, the carrier or carriersused in a composition as made according to this invention.

Numerous clays having a layered structure with interstices, andsynthetic inorganic materials that resemble such clays in respect ofchemical composition, crystallinity and layered morphology, are suitablefor use herein as carriers. Suitable clays having a layered structurewith interstices include smectite, kaolin, muscovite, vermiculite,phlogopite, xanthophyllite, and chrysotile, and mixtures thereof.Preferred are smectite clays and kaolin clays. Smectite clays includemontmorillonite, beidellite, nontronite, saponite, hectorite, sauconite,and others. Kaolin clays include kaolinite, deckite, nacrite,antigorite, and others. Most preferred is montmorillonite. Averageparticle sizes range from 0.5 to 50 micrometers.

Desirable properties of an insect/arthropod repellant composition,particularly one to be applied to the skin or other surface of ananimate host, include low toxicity, resistance to loss by waterimmersion or sweating, low or no odor or at least a pleasant odor, easeof application, and rapid formation of a dry tack-free surface film. Acomposition possessing these properties enables treatment of adomesticated animal infested with an insect/arthropod (e.g. dogsinfested with fleas, poultry infested with lice, or cattle infested withhorn flies or ticks), or a human experiencing unavoidable exposure to aninsect/arthropod, by contacting the skin, hide, hair, fur, feathers orother surface with an amount of the composition effective to repel theinsect/arthropod from the host.

The application of an effective amount of an repellant composition on asurface subject to attack by an insect/arthropod (such as the skin,hide, hair, fur, or feathers of an animate host, or the stalks, stems,leaves or flowers of a plant or crop) may be accomplished by dispersingthe composition into the air, or by dispersing the composition as aliquid mist or incorporated into a powder or dust, and this will permitthe composition to fall on the desired surfaces of a host. It may alsobe desirable to formulate a repellent composition by combining apreparation hereof with a fugitive vehicle for application in the formof a spray. Such a composition may be an aerosol, sprayable liquid orsprayable powder composition adapted to disperse the active ingredientinto the atmosphere by means of a compressed gas, or a mechanical pumpspray. Likewise, directly spreading a liquid/semi-solid/solid repellenton a host in wet or dry form (as a friable solid, for example) is auseful method of contacting a surface of the host with an effectiveamount of the repellent.

Further, it may also be desirable to combine a preparation hereof withone or more other compounds known to have insect repellency in acomposition to achieve a synergistic effect. Suitable insect repellantcompounds combinable for such purpose include nepetalactones,nepetalactams, dihydronepetalactones and derivatives thereof,dihydronepetalactams and derivatives thereof, benzil, benzyl benzoate,2,3,4,5-bis(butyl-2-ene)tetrahydrofurfural, butoxypolypropylene glycol,N-butylacetanilide,normal-butyl-6,6-dimethyl-5,6-dihydro-1,4-pyrone-2-carboxylate, dibutyladipate, dibutyl phthalate, di-normal-butyl succinate,N,N-diethyl-meta-toluamide, dimethyl carbate, dimethyl phthalate,2-ethyl-2-butyl-1,3-propanediol, 2-ethyl-1,3-hexanediol,di-normal-propyl isocinchomeronate, 2-phenylcyclohexanol,p-methane-3,8-diol, and normal-propyl N,N-diethylsuccinamate.

In addition to one or more of the preparations hereof, aninsect/arthropod repellent composition may also include one or moreessential oils and/or active ingredients of essential oils. An essentialoil includes any type of volatile oil that is obtained from a plant andpossesses the odor and other characteristic properties of the plant.Examples of useful essential oils include: almond bitter oil, anise oil,basil oil, bay oil, caraway oil, cardamom oil, cedar oil, celery oil,chamomile oil, cinnamon oil, citronella oil, clove oil, coriander oil,cumin oil, dill oil, eucalyptus oil, fennel oil, ginger oil, grapefruitoil, lemon oil, lime oil, mint oil, parsley oil, peppermint oil, pepperoil, rose oil, spearmint oil (menthol), sweet orange oil, thyme oil,turmeric oil, and oil of wintergreen. Examples of active ingredients inessential oils are: citronellal, methyl salicylate, ethyl salicylate,propyl salicylate, citronellol, safrole, and limonene.

The insects and arthropods that may be repelled by the preparationshereof include any member of a large group of invertebrate animalscharacterized, in the adult state (non-adult insect states include larvaand pupa) by division of the body into head, thorax, and abdomen, threepairs of legs, and, often (but not always) two pairs of membranouswings. This definition therefore includes a variety of biting insects(e.g. ants, bees, chiggers, fleas, mosquitoes, ticks, wasps), bitingflies [e.g. black flies, green head flies, stable flies, horn flies(haematobia irritans)], wood-boring insects (e.g. termites), noxiousinsects (e.g. houseflies, cockroaches, lice, roaches, wood lice), andhousehold pests (e.g. flour and bean beetles, dust mites, moths,silverfish, weevils).

In another embodiment, a preparation hereof may be used as a fragrancematerial or as an active in a fragrance composition, and be applied in atopical manner to human or animal skin or hair to impart a pleasingscent or aroma thereto, as in colognes or perfumes for humans or pets.Alternatively, the pleasing scent or aroma may be obtained by the use ofa preparation hereof as an insect/arthropod repellant where thepreparation has the dual attributes of simultaneously imparting bothrepellency as well as the pleasing scent or aroma.

In a further embodiment, the insect/arthropod repellency and/orfragrance of products directed to other fundamental purposes will beimproved by the presence therein of a preparation of this invention.Those other products include, for example, a body wash, rinse, lotion,splash, tonic or toner, bath and shower gels, foam products (e.g.shaving foams), makeup, deodorants, shampoo, hair lacquers/hair rinses,personal soap compositions (e.g. hand soaps and bath/shower soaps) orother personal care treatments or palliatives, and cleaning agents suchas detergents and solvents, and air fresheners and odor removers. Suchproducts may be fabricated, for example, in the form of a sprayableliquid, an aerosol, a foam, a cream, an ointment, a gel, a paste, apowder or a friable solid. The process of fabricating such a productwould thus include admixing a preparation hereof with suitable carriersor other inert ingredients to facilitate delivery in the physical formas described, such as liquid carriers that are readily sprayed; apropellant for an aerosol or a foam; viscous carriers for a cream, anointment, a gel or a paste; or dry or semi-solid carriers for a powderor a friable solid.

Any of the above described products may also contain othertherapeutically or cosmetically active adjuvants or supplementalingredients as are typical in the personal care industry. Examples ofthese include fungicides, sunscreening agents, sunblocking agents,vitamins, tanning agents, plant extracts, anti-inflammatory agents,anti-oxidants, radical scavenging agents, retinoids, alpha-hydroxyacids, antiseptics, antibiotics, antibacterial agents, antihistamines;adjuvants such as thickeners, buffering agents, chelating agents,preservatives, gelling agents, stabilizers, surfactants, emolients,coloring agents, aloe vera, waxes, and penetration enhancers; andmixtures of any two or more thereof.

Inanimate hosts into which a preparation hereof may be incorporated toproduce an insect/arthropod repellent effect, or to impart an improvedfragrance, include articles or manufactured goods such as textile andfibrous goods, clothing, sanitary goods, carpeting, linens, outdoor ormilitary equipment such as tents, tarpaulins, backpacks or mosquitonetting, candles, paper, paint, ink, wood products such as furniture,plastics and other polymers, and the like.

A preparation hereof may be formulated as or incorporated into acomposition for application to an animate host by any of the samemethods known in the cosmetics industry, such as dilution, mixing,thickening, emulsifying, bottling and pressurizing. A preparation hereofmay be incorporated into an article that serves as an inanimate host bymixing during production or by post-production steps such as spraying ordipping.

A preparation hereof may be admixed in a composition with othercomponents, such as a carrier, in an amount that is effective for usagefor a particular purpose, such as an insect/arthropod repellant,fragrance or other skin treatment. The amount of a HRP as describedherein, contained in a composition will generally not exceed about 80%by weight based on the weight of the final product, however, greateramounts may be utilized in certain applications, and this amount is notlimiting. More preferably, a suitable amount of a HRP will be at leastabout 0.001% by weight and preferably about 0.01% up to about 50% byweight; and more preferably, from about 0.01% to about 20% weightpercent, based on the total weight of the total composition or article.Specific compositions will depend on the intended use.

Other compositions, materials and methods relevant to the use of a HRPare as disclosed in US 2003/062,357; US 2003/079,786; US 2003/191,047;and US 2006/148,842, each of which is incorporated in its entirety as apart hereof for all purposes.

A hydrogenated catmint oil obtainable by one or more of the processes ofthis invention may be incorporated into a formulated product forapplication to the skin, hide, hair, fur or feathers of a human ordomesticated animal. For such purpose, the formulated product maycontain one or more adjuvants or other ingredients as common for use inthe cosmetics industry, including those disclosed in U.S. applicationSer. No. 11/266,641, and U.S. Provisional Application No. 60/799,277,each of which is incorporated in its entirety as a part hereof for allpurposes.

Where a range of numerical values is recited herein, the range includesthe endpoints thereof and all the individual integers and fractionswithin the range, and also includes each of the narrower ranges thereinformed by all the various possible combinations of those endpoints andinternal integers and fractions to form subgroups of the larger group ofvalues within the stated range to the same extent as if each of thosenarrower ranges was explicitly recited. Where a range of numericalvalues is stated herein as being greater than a stated value, the rangeis nevertheless finite and is bounded on its upper end by a value thatis operable within the context of the invention as described herein.Where a range of numerical values is stated herein as being less than astated value, the range is nevertheless bounded on its lower end by anon-zero value.

In this specification, unless explicitly stated otherwise or indicatedto the contrary by the context of usage, amounts, sizes, ranges,formulations, parameters, and other quantities and characteristicsrecited herein, particularly when modified by the term “about”, may butneed not be exact, and may also be approximate and/or larger or smaller(as desired) than stated, reflecting tolerances, conversion factors,rounding off, measurement error and the like, as well as the inclusionwithin a stated value of those values outside it that have, within thecontext of this invention, functional and/or operable equivalence to thestated value.

In this specification, unless explicitly stated otherwise or indicatedto the contrary by the context of usage, where an embodiment of thesubject matter hereof is stated or described as comprising, including,containing, having, being composed of or being constituted by or ofcertain features or elements, one or more features or elements inaddition to those explicitly stated or described may be present in theembodiment. An alternative embodiment of the subject matter hereof,however, may be stated or described as consisting essentially of certainfeatures or elements, in which embodiment features or elements thatwould materially alter the principle of operation or the distinguishingcharacteristics of the embodiment are not present therein. A furtheralternative embodiment of the subject matter hereof may be stated ordescribed as consisting of certain features or elements, in whichembodiment, or in insubstantial variations thereof, only the features orelements specifically stated or described are present.

What is claimed is:
 1. A process for preparing hydrogenated catmint oil comprising: (a) distilling crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from the beginning amount of crude catmint oil, and (ii) a pot fraction; and (b) contacting the pot fraction of step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; wherein one or both of steps (a) and (b) are conducted in the presence of a solvent.
 2. The process of claim 1 wherein the distillation of step (a) is conducted in the presence of a solvent.
 3. The process of claim 1 wherein the hydrogenation of step (b) is conducted in the presence of a solvent.
 4. The process of claim 1 wherein the distillation of step (a) and the hydrogenation of step (b) are both conducted in the presence of a solvent.
 5. The process of claim 1 wherein solvent is added to the pot fraction produced by step (a) before it is hydrogenated in step (b).
 6. The process of claim 1 wherein solvent is present in the hydrogenated catmint oil produced in step (b), and the process further comprises a step of removing solvent from the hydrogenated catmint oil produced in step (b).
 7. The process of claim 6 further comprising a step of recycling removed solvent to the distillation of step (a) and/or the hydrogenation of step (b).
 8. The process of claim 1 wherein the hydrogenation of step (b) is conducted in the presence of solvent; is conducted in a plurality of steps, reactor zones or reactors; and solvent is removed between one step, zone or reactor and the next succeeding step, zone or reactor.
 9. The process of claim 8 further comprising a step of recycling removed solvent to the distillation of step (a) and/or the hydrogenation of step (b).
 10. The process of claim 1 further comprising a step of incorporating the hydrogenated catmint oil produced in step (b) into a formulated product for application to the skin, hide, hair, fur or feathers of a human or domesticated animal.
 11. A process for preparing a product formulated from a hydrogenated catmint oil, comprising: (a) distilling a beginning amount of crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from the beginning amount of crude catmint oil, and (ii) a pot fraction; (b) contacting the pot fraction of step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; and (c) incorporating the hydrogenated catmint oil produced in step (b) into a formulated product for application to the skin, hide, hair, fur or feathers of a human or domesticated animal; wherein the distillation of step (a) and/or the hydrogenation of step (b) is conducted in the presence of a solvent.
 12. The process of claim 11 further comprising a step of incorporating a solvent into the formulated product.
 13. The process of claim 12 wherein the incorporation of solvent into the formulated product comprises a step of adding solvent to the distillation that occurs during step (a).
 14. The process of claim 12 wherein the incorporation of solvent into the formulated product comprises a step of adding solvent to the hydrogenation that occurs during step (b).
 15. The process of claim 13 wherein the incorporation of solvent into the formulated product comprises a step of adding solvent to the hydrogenated catmint oil that is obtained as the product of step (b).
 16. The process of claim 12 wherein the incorporation of solvent into the formulated product comprises any two of, or all three of, the steps of (i) adding solvent to the distillation that occurs in step (a), (ii) adding solvent to the hydrogenation that occurs during step (b), and (ii) adding solvent to the hydrogenated catmint oil that is obtained as the product of step (b).
 17. The process of claim 16 wherein the same solvent is used in all steps.
 18. The process of claim 11 wherein the hydrogenation of step (b) is conducted in a plurality of steps, reactor zones or reactors, and the hydrogenation is conducted in the presence of solvent in some but not all, or in all, of the steps, zones or reactors.
 19. The process of claim 12 wherein the hydrogenation of step (b) is conducted in a plurality of steps, reactor zones or reactors, and the incorporation of solvent into the formulated product comprises a step of adding solvent to the hydrogenation that occurs in some but not all, or in all, of the steps, zones or reactors. 